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41.
Severe myoclonic epilepsy (SMEI) or Dravet syndrome is caused by mutations of the SCN1A gene that encodes voltage-gated sodium channel alpha-1 subunit. Recently, we generated and characterized a knock-in (KI) mice with an SCN1A nonsense mutation that appeared in three independent SMEI patients. The SCN1A-KI mice well reproduced the SMEI disease phenotypes. Both homozygous and heterozygous knock-in mice developed epileptic seizures within the first postnatal month. In heterozygous knock-in mice, trains of evoked action potentials in inhibitory neurons exhibited pronounced spike amplitude decrement late in the burst but not in pyramidal neurons. We further showed that in wild-type mice the Nav1.1 protein is expressed dominantly in axons and moderately in somata of parbalbumin (PV) – positive inhibitory interneurons. Our immunohistochemical observations of the Nav1.1 are clearly distinct to the previous studies, and our findings has corrected the view of the Nav1.1 protein distribution. The data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice. These information should contribute to the understanding of molecular pathomechanism of SMEI and to develop its effective therapies. 相似文献
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43.
U. Logonder Z. Jenko-Pranikar T. Scott-Davey J. Punger
ar I. Kriaj J.B. Harris 《Experimental neurology》2009,219(2):591-594
A mutant form of ammodytoxin A, a neurotoxic phospholipase A2 from the venom of the long nosed viper Vipera ammodytes ammodytes, was prepared by site-directed mutagenesis, conjugated to a nanogold particle and inoculated into the antero-lateral aspect of one hind limb of female mice. Eight hours later the mice were killed, the soleus muscles of both ipsi- and contra-lateral hind limbs were removed, exposed to a silver enhancing medium and then prepared for transmission electron microscopy. Silver-enhanced particles were subsequently found concentrated in the peri-synaptic area, particularly within the synaptic gutter and the deep synaptic folds, and in many cases had been taken up into the cytoplasm of the terminal boutons of the motor axon. The results suggest that the presynaptic neurotoxicity of snake venom phospholipases A2 involves several components of the neuromuscular apparatus, including intracellular organelles of the motor nerve terminal. 相似文献
44.
45.
HELENA MARKKANEN STINA M. SYRJÄNEN PEKKA ALAKUIJALA 《European journal of oral sciences》1986,94(2):115-120
Abstract — The concentrations of IgA, lysozyme and β-microglobulin (β2 -m) were quantitated in wax-stimulated mixed saliva from 28 patients with severe periodontitis and from 28 healthy controls. The mutual correlations between IgA, lysozyme and β2 -rn were determined. In patients with periodontitis decreased lysozyme concentrations were detected when compared with controls (P<0.05). The correlation between IgA and β2 -m concentrations was highly significant in both groups studied (P<0.0001, and P <0.002), whereas β2 -m and lysozyme concentrations were positively correlated in patients but not in controls. In addition, a significant correlation between IgA and lysozyme was found only in periodontal patients ( P <0.001). 相似文献
46.
Objective To investigate the best way to control the blood sugar level during the perioperation of bone fracture patients with type 2 diabetes(T2DM).Methods Bone fracture patients with T2DM were randomly divided into three groups:continuous subcutaneous insulin infusion group(insulin aspart,group CSII,n=20),glargine treatment group(insulin aspart+insulin glargine,group GA,n=20),and NPH treatment(insulin aspart+rh-insulin,group NA,n=20).The levels of fasting plasma glucose(FPG)and the 2 hours postprandial glucose(2h PG),blood glucose fluctuation(BGF),insulin dosage(ID),good effective time(GET),incidence of hypoglycemia,dawn phenomenon and infection,average time of stitches removal(ATSR),average hospitalized length(AHL)of three groups were compared.Results FPG and 2hPG,ID in group CSII[(6.32±1.18)mmol/L,(7.72±1.53)mmol/L,(35.40±1.60)IU]and group GA [(6.25±0.88)mmol/L,(7.32±1.17)mmol/L,(36.20±0.80)IU]were significantly lower than those of group NA [(7.44±1.36)mmol/L,(8.52±0.76)mmol/L,(40.50±2.40)IU,all P<0.05],simulaneously,BGF,GET incidence of complications,ATSR,AHL of group CSII and GA were significantly lower than those of group NA(all P<0.05).There were not significant difference between group CSII and group GA.Compared with group CSII,group GA had less costs in-hospital and better practicability.Conclusion Both CSII and insulin glargine combined with insulin aspart can effectively,safely,rapidly and stablely control hyperglycemia.and might be the first choice to control blood sugar for bone fracture patients with T2DM in perioperation. 相似文献
47.
子宫腺肌症病变中雌激素、孕激素、癌基因、凋亡抑制基因的表达研究 总被引:1,自引:1,他引:0
目的 研究雌激素(ER)、孕激素(PR)及癌基因(cerbB-2)、凋亡抑制基因(Bcl-2)在子宫腺肌症病变中的表达和子宫腺肌症发病的相关性。方法 用免疫组化方法检测40例子宫腺肌症病变组织中ER及其他生物学指标的表达。结果 ER、PR与CerbB.2、Bcl-2在子宫腺肌症病变中均有不同程度的阳性表达,子宫肌层异位内膜ER阳性表达率97.5%,PR阳性率97.5%,cerbB-2阳性率82.5%,Bcl-2阳性率62.5%。在位内膜和异位内膜ER、PR均呈阳性,阳性率比较差异无统计学意义(P〉0.05)。异位内膜cerbB-2的强阳性率高于在位内膜,差异有统计学意义(P〈0.05)。ER、PR与cerbB-2、Bcl-2阳性率相比具有相关性(P〈0.05)。结论 ER、PR与cerbB.2、Bcl-2在异位内膜高表达,提示这些生物学指标在子宫腺肌症发生发展中发挥作用。 相似文献
48.
X Dong M He X Song B Lu Y Yang S Zhang N Zhao L Zhou Y Li X Zhu R Hu 《Diabetic medicine》2007,24(12):1482-1486
AIMS: Our aim was to assess performances of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease (MDRD) formulae in estimating glomerular filtration rate (GFR) in Chinese diabetic populations and their association with vascular risks. METHODS: A total of 1009 patients with Type 2 diabetes were categorized into low estimated GFR groups (GFR < 60 ml/min/1.73 m(2)) and control groups by the two equations. The performances of these formulae were assessed at different stages of kidney function. Carotid artery intima-media thickness (IMT) and the prevalence of diabetic retinopathy or albuminuria were compared among the groups. The ability of these formulae to identify established vascular risk markers using sensitivity, specificity, positive and negative predictive values were also compared. RESULTS: The prevalence of low estimated GFR was 32.7% with the Cockcroft-Gault formula and 5.2% with the MDRD formula, respectively. In low estimated GFR subjects by the MDRD formula, IMT was significantly thicker than those by the Cockcroft-Gault formula (1.2 mm vs. 1.0 mm; P < 0.05), with a higher prevalence of albuminuria (78.4 vs. 52.8%, P < 0.05) and diabetic retinopathy (46.5 vs. 30.5%; P < 0.05). The Cockcroft-Gault formula gave a specificity of 71.7% and a sensitivity of 37.0%, and the MDRD formula gave a specificity of 96.6% and a sensitivity of 7.9% in estimating low GFR relevant for established vascular risks. CONCLUSIONS: These formulae performed differently in Chinese diabetic populations. The simplified MDRD formula is minimally superior to the Cockcroft-Gault formula for its high specificity and positive predictive values in estimating low GFR relevant for vascular risks. 相似文献
49.
目的探讨复方丹参注射液联合干扰素治疗慢性乙肝患者的疗效。方法110例慢性乙肝患者,按随机方法分成①对照组30例,应用普通保肝药物治疗,疗程6个月;②丹参组30例,应用复方丹参注射液(每ml含丹参、降香各1g)30ml加入10%葡萄糖溶液300ml中静脉注射1个月;③IFN组30例,应用IFN—α 3MU,隔日一次肌内注射,3个月;④联合组20例,应用复方丹参注射液30ml加10%葡萄糖溶液300ml静脉注射1个月,IFN-α 3MU,隔日一次肌内注射,3个月。丹参组,IFN组和联合组保肝药物治疗同对照组。四组病例在性别、年龄、病程,治疗前肝功能等方面均无统计学差异。治疗前检测肝功能,肝炎病毒标志,血清HA、IV—C、PCI—Ⅱ,部分病例进行肝穿病理检查。治疗开始后每月检测肝功能,3个月(治疗后)和6个月(随访时)时检测血清HA、IV—C、PCⅢ及乙肝病毒标志,治疗后1年行肝穿病理检查。结果治疗前四组患者血清HA、PCⅢ、IV—C水平无统计学差异;治疗后丹参组、IFN组、联合组血清HA、FCⅢ、IV—C水平较治疗前及对照组有不同程度的降低。结论复方丹参注射液联合IFN治疗可使血清HA、PCⅢ、IV—C有明显下降,肝组织病理改变明显改善,为目前有效的慢性乙肝治疗措施。 相似文献
50.
Recent work demonstrated that crotoxin, the main toxin of Crotalus durissus terrificus venom, inhibits macrophage spreading and phagocytic activities. The crotoxin molecule is composed of two subunits, an acidic non-toxic and non-enzymatic polypeptide named crotapotin and a weakly toxic basic phospholipase A2 (PLA2). In the present work, the active subunit responsible for the inhibitory effect of crotoxin on macrophage function was investigated. Peritoneal macrophages harvested from naive rats were used. Crotapotin (2.12, 3.75, or 8.37 nM/ml), added for 2 h to the medium of peritoneal cell incubation, did not modify the spreading and phagocytic activities of these cells. On the other hand, the PLA2 (1.43, 2.86, or 6.43 nM/ml) subunit caused a significant reduction (30, 33, and 35%, respectively) of the spreading activity. The PLA2 also inhibited the phagocytosis of opsonised zymosan, opsonised sheep erythrocytes, and Candida albicans, indicating that this inhibitory effect is not dependent on the type of receptor involved in the phagocytosis process. The inhibitory effect of PLA2 was not due to loss of cell membrane integrity, since macrophage viability was higher than 95%. These findings indicate that the inhibitory effect of crotoxin on macrophage spreading and phagocytic activities is caused by the phospholipase A2 subunit. 相似文献